1. Field of the Invention
This invention is directed to methods for increased longevity, delay of aging associated disorders, protection from acute physical stress and induction of regeneration and healing by administration of Long chain Free Fatty Acids (LFFA) and CoA derivatives of Long chain Free Fatty Acids (CoALFFA) in mammals.
2. Review of Related Art
Sixty years of active investigation has conclusively demonstrated that reduced caloric intake extends life span in a wide variety of animal species, including mammals (e.g., mice and rats) (Ingram, D. K. et al., “The Potential for Nutritional Modulation of the Aging Process,” Food and Nutrition Press (1991)). Moreover, the incidence of pathologies associated with aging in rodents are also delayed by caloric restriction (CR) (Roth, G. S. et al., Nature Medicine 1:414-415 (1995) and Weindruch, R., Scientific American: 46-52 (January 1996)) More recently, on-going CR studies using primates seem to mimic comparable biochemical changes observed in rodents (Roth, et al., 1995), and, by extension, the same effects should be expected to occur in humans subjected to caloric restriction.
Several hypotheses have been proposed to explain the mechanism(s) underlying the beneficial effects of CR, and some of these have been discarded. Today, it is accepted that the anti-aging effects of CR are not mediated by a retardation in growth and development, or by a reduction in body fat of animals subjected to caloric restriction. Still under investigation is the hypothesis that the beneficial effects of CR are due to a reduction in oxidative damage secondary to the generation of oxygen radicals (Weindruch, R., 1996). Support for this hypothesis is derived from studies demonstrating a reduction in lipid peroxidation and induction of the enzyme Superoxide Dismutase (Heydari, A. R. et al., Annals N.Y. Academy Science 663-384-395 (1992) and Yu, B. P., “Free Radicals in Aging” CRC Press (1993)) in animals subjected to caloric restriction. Another hypothesis that has received considerable attention attributes the beneficial effects of CR to the induction of “protective genes”. Investigators pursuing this hypothesis have demonstrated the induction of genes coding for SOD, HRP-70 and A2u-globulin and concluded that the effects of CR regulate gene expression at the transcriptional level (Heydari, A. R. et al., (1992). Most recently, using a genomics based approach to analyze gene expression in the skeletal muscles of aged and CR mice, it was proposed that CR retards the aging process by causing a metabolic shift resulting in increased protein turnover and decreased macromolecular damage (Lee, et al., 1999, Science, 285:1390-1393).
Although it is likely that protection against oxidative damage, and the induction of protective genes may play a role in the beneficial effects of CR, the underlying mechanism(s) involved remain a mystery.